1. Field of the Invention
The present invention relates to a method for producing a 1,2-dihydropyridine-2-one compound represented by formula (III) which comprises reacting a compound represented by formula (I) with a boronic acid derivative represented by formula (II) in the presence of a palladium compound, a copper compound, a phosphorus compound and a base. Further, the present invention relates to crystals of 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridine-2-one and a method for producing the crystals.
The compound of formula (III) represented by 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridine-2-one is useful as, for example, a therapeutic agent for diseases such as Parkinson's disease, multiple sclerosis, epilepsy, etc.
2. Description of the Related Art
Background art concerning a method for producing the compound of formula (III) is explained below.
In the production method 2 in WO 01/96308, the coupling reaction of a compound (viii) with an arylboronic acid derivative by the use of a palladium catalyst is described as to a final step for producing a compound (I-1), but the reaction in the presence of a palladium compound, a copper compound and a phosphorus compound is neither suggested nor described which is characteristic of the present invention.
Production Method 2

Also in the production method 3 in WO 01/96308, the coupling reaction of a compound WO with an arylboronic acid derivative by the use of a palladium catalyst is described as to a final step for producing a compound (I-1), but the reaction in the presence of a palladium compound, a copper compound and a phosphorus compound is neither suggested nor described which is characteristic of the present invention.
Production Method 3

The compound of formula (III-a) described hereinafter is a well-known compound. In Example 7 in WO 01/96308, it is known that as shown in the following reaction scheme, this compound may be produced by reacting 3-(2-cyanophenyl)-5-(2-pyridyl)-2(1H)-pyridone with phenylboronic acid in the presence of copper acetate and triethylamine. But, there is neither suggested nor described a method for producing a compound of formula (III) by the reaction of a compound of formula (I) with a compound of formula (II) in the presence of a palladium compound, a copper compound, a phosphorus compound and a base which is characteristic of the present invention.

As to the compound of formula (I) represented by 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridine-2-one (III-a), a method for producing this compound is described in claim 49 and Example 404 in WO 01/96308.
On the other hand, the effect of a copper catalyst in the Suzuki reaction is described in G. M. Boland et al., J. Chem. Soc., Perkin Trans. 1, 2591-2587(1996). Although this reference describes “Pd(PPh3)4-CuI”, copper iodide is used in a large amount of 1.1 equivalents per equivalent of a starting material in the reference. The reference neither suggests nor describes the progress of the reaction in the presence of a palladium compound, a copper compound and a phosphorus compound, in particular, the reaction in the presence of a catalytic amount of the copper compound, which is characteristic of the present invention.
On the other hand, among the compounds of formula (III), particularly, 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one (hereafter referred to as Compound (A) in some cases) shows significant antagonistic action against AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor (see WO 01/96308).
Although Example 7 in WO 01/96308 discloses a process for producing the compound (A), there is merely described, “the residue is purified by silica gel column chromatography (ethyl acetate/hexane=1:2)” and there is no disclosure of the form of the obtained compound.